Glucose stimulation induces dynamic change of mitochondrial morphology to promote insulin secretion in the insulinoma cell line INS-1E

Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e60810-e60810
Main Authors: Jhun, Bong Sook, Lee, Hakjoo, Jin, Zheng-Gen, Yoon, Yisang
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Apoptosis
ATP
Biology
Calcium - metabolism
Calcium influx
Cell Line, Tumor
Cytology
Dentistry
Depolarization
Diabetes
Exocytosis
Fission
Genetic aspects
Glucose
Glucose - pharmacology
Glucose metabolism
Humans
Insulin
Insulin - metabolism
Insulin Secretion
Insulinoma
Insulinoma - metabolism
Medicine
Membrane potential
Metabolism
Mitochondria
Mitochondrial DNA
Morphology
Neuroendocrine tumors
Pancreas
Pancreatic beta cells
Physiological aspects
Physiology
Rodents
Secretion
Stimulation
Tubules
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Summary:Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change and, importantly, blocked GSIS. We found that abolishing mitochondrial morphology change in glucose stimulation increased the mitochondrial inner membrane proton leak, and thus significantly diminished the mitochondrial ATP producing capacity in response to glucose stimulation. These results demonstrate that dynamic change of mitochondrial morphology is a previously unrecognized component for metabolism-secretion coupling of pancreatic β-cells by participating in efficient ATP production in response to elevated glucose levels.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0060810